The role of astrocytes (sub)types in adult brain plasticity

Astrocytes are the most abundant glial cells found amidst neurons in the mammalian central nervous system (CNS). There, they establish connections not only with one another but also with neurons, creating an intricate network that allows them to modulate several CNS functions. Particularly, at the tripartite synapse, astrocytes provide neurons with structural and metabolic support and regulate synaptic activity and connectivity. Therefore, astrocytes find themselves in a privileged position to sense changes in synaptic activity and engage in processes such as neuroplasticity. Neuroplasticity refers to the structural and functional adaptation neuronal connections undergo in response to sensory stimuli. This process is particularly prominent during the developmental stages of life but also persists in adulthood, although to a lesser extent, contributing to learning, memory, and recovery from injury. Astrocytes have been shown to play critical roles in synapse formation and circuit refinement at early developmental stages, however, their role in adult brain plasticity still remains elusive. Throughout the years, the study of how the visual cortex adapts to vision loss has brought valuable insights into cortical plasticity mechanisms. Indeed, using monocular enucleation (ME) of adult mice as a model to induce irreversible vision loss from one eye, our group showed that, inhibiting astrocytes was sufficient to inhibit long-term neuronal reactivation in the deprived visual cortex, while astrocyte activation boosted neuronal recovery. Thus, these data highlights the importance of astrocytes for sensory deprivation-induced plasticity and neuronal recovery. Therefore, the project herein proposed aims at following up these observations by investigating the contribution of distinct cell (sub)types, as well as the molecular pathways and morphological changes at the tripartite synapse involved in driving cortical plasticity. With this, we hope to gain insights into the molecular strategies used by plasticity-promoting astrocytes and astrocyte-neuron network during plasticity. Ultimately, this might lead to novel therapeutical approaches for patients with late-onset sensory deprivation, and even to combat age-related brain function incapacitation.